Total submissions: 2
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Invitae | RCV001228571 | SCV001400974 | uncertain significance | Tumor predisposition syndrome 3 | 2023-05-19 | criteria provided, single submitter | clinical testing | In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is not expected to disrupt POT1 protein function. ClinVar contains an entry for this variant (Variation ID: 955860). This variant has not been reported in the literature in individuals affected with POT1-related conditions. This variant is not present in population databases (gnomAD no frequency). This sequence change replaces aspartic acid, which is acidic and polar, with tyrosine, which is neutral and polar, at codon 420 of the POT1 protein (p.Asp420Tyr). |
Ambry Genetics | RCV002429972 | SCV002680119 | uncertain significance | Hereditary cancer-predisposing syndrome | 2022-06-11 | criteria provided, single submitter | clinical testing | The p.D420Y variant (also known as c.1258G>T), located in coding exon 10 of the POT1 gene, results from a G to T substitution at nucleotide position 1258. The aspartic acid at codon 420 is replaced by tyrosine, an amino acid with highly dissimilar properties. This amino acid position is conserved. In addition, this alteration is predicted to be tolerated by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. |